title: pH/temperature sensitive magnetic nanogels conjugated with Cy5.5-labled lactoferrin for MR and fluorescence imaging of glioma in rats.
abstract: Glioma is the most common primary brain tumor and causes a disproportionate level of morbidity and mortality across a wide range of individuals. From previous clinical practices, definition of glioma margin is the key point for surgical resection. In order to outline the exact margin of glioma and provide a guide effect for the physicians both at pre-surgical planning stage and surgical resection stage, pH/temperature sensitive magnetic nanogels conjugated with Cy5.5-labled lactoferrin (Cy5.5-Lf-MPNA nanogels) were developed as a promising contrast agent. Due to its pH/te mperature sensitivity, Cy5.5-Lf-MPNA nanogels could change in its hydrophilic/hydrophobic properties and size at different pH and temperatures. Under physiological conditions (pH 7.4, 37 °C), Cy5.5-Lf-MPNA nanogels were hydrophilic and swollen, which could prolong the blood circulation time. In the acidic environment of tumor tissues (pH 6.8, 37 °C), Cy5.5-Lf-MPNA nanogels became hydrophobic and shrunken, which could be more easily accumulated in tumor tissue and internalized by tumor cells. In addition, lactoferrin, an effective targeting ligand for glioma, provides active tumor targeting ability. In vivo studies on rats bearing in situ glioma indicated that the MR/fluorescence imaging with high sensitivity and specificity could be acquired using Cy5.5-Lf-MPNA nanogels due to active targeting function of the Lf and enhancement of cellular uptake by tailoring the hydrophilic/hydrophobic properties of the nanogels. With good biocompatibility shown by cytotoxicity assay and histopathological analysis, Cy5.5-Lf-MPNA nanogels are hopeful to be developed as a specific and high-sensitive contrast agent for preoperative MRI and intraoperative fluorescence imaging of glioma.
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Jiang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Ketao
authors.initials: K
authors.lastname: Mu
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Zhu
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Huibi
authors.initials: H
authors.lastname: Xu
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001932:Brain Neoplasms / Q000175:diagnosis; D002232:Carbocyanines; D045744:Cell Line, Tumor; D005453:Fluorescence; D005910:Glioma / Q000175:diagnosis* / Q000473:pathology; D049673:History, 20th Century; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007781:Lactoferrin; D060328:Magnetic Phenomena; D008279:Magnetic Resonance Imaging; D008297:Male; D008422:Materials Testing; D051379:Mice; D041681:NIH 3T3 Cells; D000080385:Nanogels; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; C052970:poly-N-isopropylacrylamide; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D007781:Lactoferrin
keywords: Contrast agent; Fluorescence imaging; Glioma; MRI; Magnetic nanogel; pH/temperature sensitive